This is a revised application for collaborative research under the Fogarty International Program. The aim of the parent grant is to investigate the genetic architecture of odor-guided behavior in Drosophila melanogaster, a behavior which is essential for survival and reproduction. When assessing the genetic basis of any complex trait, it is important to distinguish genes that contribute to manifestation of the trait and a subset of these genes that contribute to naturally occurring phenotypic variation of the trait, as the latter harbor polymorphisms that serve as the substrate for evolution. The specific aims of the parent grant focus entirely on adult flies, i.e. the reproductive phase of the life cycle. The present Fogarty application proposes to identify novel genes that contribute to larval odor-guided behavior and to assess which of these genes may contribute to phenotypic plasticity in natural populations. The specific aims of this Fogarty proposal are: (1) Identification of genes that contribute to odor-guided behavior in Drosophila melanogaster larvae; and, (2) Identification of those genes, identified in Specific Aim 1, that contribute to phenotypic variation for larval olfactory behavior in natural populations and form the substrate for adaptive evolution. Co-isogenic P- element insertion lines will be screened to identify genes that affect olfactory behavior in larvae, and candidate genes responsible for larval smell impairment will be compared to those that affect odor-guided behavior in adult flies identified earlier from a screen of the same P-element insertion lines. Individual chromosomes from eight diverse natural populations of D. melanogaster from Argentina will be substituted into an isogenic background and quantitative complementation tests will be performed to assess for up to 12 larval genes identified in Specific Aim 1 whether these genes contribute to natural variation in olfactory behavior. The proposed approach will significantly extend the parent grant and is innovative in that it combines quantitative genetic strategies directly with molecular ecology in the context of chemosensation.